DESCRIPTION (Applicant's Description): The broad objective of this application is to determine the developmental relationships among populations of cells in the hindbrain and the craniofacial tissues of mammals. The development these tissues are inextricably linked to one another by the migration of neural crest cells from the hindbrain to form much of the skeletal and connective tissue elements of the head and neck. In this manner some of the positional information encoded by restricted patterns of gene expression in the hindbrain and which guides its development, is also projected onto nascent craniofacial tissues. It is generally agreed that members of the Hox gene family contribute to the genetic specification of hindbrain and craniofacial tissues. Here we propose to use a novel lineage marking paradigm to determine the fates of cells that express specific Hox genes, both in the context of the normal animal and in mice in which the function of the Hox gene is altered. In some cases the alteration will include the complete elimination of gene function. We will also examine the alterations in Hox gene function occasioned by the elimination of individual members of the Meis gene family, which are known to collaborate with Hox genes in the patterning of appendages, and which may well also contribute to the patterning of the hindbrain and craniofacial tissues.